Reduxin, 10 mg+158, 5 mg capsules 30 pcs

A combined medication for the treatment of obesity, the action of which is due to its constituent components. Sibutramine is a prodrug and shows its action in vivo due to metabolites (primary and secondary amines) inhibiting monoamine reuptake (mainly serotonin and noradrenaline).

The increase of neurotransmitters in synapses increases the activity of central serotonin 5-HT receptors and adrenoreceptors, which contributes to an increased feeling of satiety and decreased need for food, as well as increased thermoreduction. By activating β3-adrenoceptors indirectly, sibutramine affects brown adipose tissue. Reduction of body weight is accompanied by an increase in the serum concentration of HDL and a decrease in triglycerides, total cholesterol, LDL, and uric acid.

Sibutramine and its metabolites do not affect the release of monoamines, do not inhibit MAO; have no affinity for a large number of neurotransmitter receptors, including serotonin receptors (5-HT1, 5-HT1A, 5-HT1B, 5-HT2A, 5-HT2C), adrenoreceptors (β1, β2, β3, α1, α2), dopamine (D1, D2), muscarinic, histamine (H1), benzodiazepine and NMDA receptors.

Microcrystalline cellulose is an enterosorbent, has sorption properties and non-specific detoxifying action. It binds and removes from the body various microorganisms, products of their vital functions, toxins of exogenous and endogenous nature, allergens, xenobiotics as well as excess of certain metabolic products and metabolites responsible for the development of endogenous toxicosis.

Pharmacokinetics

Absorption, distribution, metabolism

After oral administration of the drug sibutramine is rapidly absorbed from the GI tract, not less than 77%. It is subjected to the effect of “first passage” through the liver and is biotransformed with the participation of cytochrome P450 isoenzyme 3A4 to form two active metabolites (mono- and didesmethylsibutramine).

After a single dose of 15 mg, the Cmax of monodesmethylsibutramine is 4 ng/mL (3.2-4.8 ng/mL), that of didesmethylsibutramine is 6.4 ng/mL (5.6-7.2 ng/mL). Cmax of sibutramine is reached in 1.2 h, active metabolites – in 3-4 h. Administration simultaneously with food decreases Cmax of metabolites by 30% and increases the time of its achievement by 3 hours, without changing the AUC. It is rapidly distributed in the tissues. The binding of sibutramine to plasma proteins is 97%, and that of mono- and didesmethylsibutramine – 94%. Css of active metabolites in the blood is reached within 4 days after the start of treatment and is about 2 times higher than the plasma level after a single dose.

T1/2 of sibutramine is 1.1 h, monodesmethylsibutramine 14 h, didesmethylsibutramine 16 h. Active metabolites undergo hydroxylation and conjugation to form inactive metabolites, which are eliminated mainly by the kidneys.

Indications

Type 2 Diabetes, Obesity

For weight loss in the following conditions:

– Alimentary obesity with a body mass index (BMI) of 30 kg/m2 or more;

– Alimentary obesity with a BMI of 27 kg/m2 or more in combination with other risk factors due to excess body weight (type 2 diabetes/insulin-independent/ or dyslipoproteinemia).

Composition

Active ingredients:

Sibutramine hydrochloride monohydrate – 10 mg

Microcrystalline cellulose – 158.5 mg

Additives:

Calcium stearate – 1.5 mg

Capsule composition:

Titanium dioxide – 2.0000%, Azorubin dye – 0.0041%, Brilliant blue dye – 0.0441%, Gelatin – up to 100%.

How to take, the dosage

Reduxin® is prescribed orally once daily. The dose is established individually, depending on tolerability and clinical efficacy. The recommended starting dose is 10 mg; in case of poor tolerance, a dose of 5 mg may be taken. Capsules should be taken in the morning, without chewing and with plenty of liquid. The drug can be taken both on an empty stomach and in combination with a meal.

If within 4 weeks of starting treatment 5% or more weight loss has not been achieved, the dose is increased to 15 mg/day. The duration of therapy with Reduxin should not exceed 3 months in patients who do not respond well to therapy (i.e., who do not achieve a 5% weight loss from baseline body weight within 3 months of treatment). Treatment should not be continued if the patient regains 3 kg or more in body weight during further therapy (after the achieved weight loss).

The total duration of therapy should not exceed 2 years, because there are no data on efficacy and safety for longer periods of sibutramine.

The therapy with Reduxin should be performed by a physician who has practical experience in the treatment of obesity. Taking the drug should be combined with diet and exercise.

Special Instructions

Reduxin® should only be used when all non-medicinal weight loss measures are ineffective – if the weight loss within 3 months is less than 5 kg.

The treatment with Reduxin® should be used as part of a comprehensive weight loss therapy under the supervision of a physician with practical experience in the treatment of obesity.

The complex treatment of obesity includes both changing diet and lifestyle and increasing physical activity. An important component of therapy is the creation of the prerequisites for lasting changes in eating and lifestyle habits, which are necessary to maintain the achieved weight loss even after withdrawal of drug therapy. Patients need to change their lifestyle and habits as part of therapy with Reduxin® in such a way as to ensure that the achieved weight loss is maintained after treatment completion. Patients should be clear that failure to comply with these requirements will result in weight gain again and repeat visits to the attending physician.

Patients taking Reduxin® should have their BP and HR measured. These parameters should be monitored every 2 weeks in the first 2 months of treatment and then monthly. In patients with arterial hypertension (who have a blood pressure higher than 145/90 mmHg on antihypertensive therapy) this monitoring should be particularly careful and, if necessary, at shorter intervals. In patients whose BP exceeded 145/90 mmHg twice at repeat measurements, treatment with Reduxin® should be suspended.

Particular caution is required when concomitant administration of drugs that prolong the QT interval. These drugs include histamine H1-receptor blockers (astemizole, terfenadine); antiarrhythmic QT interval prolongers (amiodarone, quinidine, flecainide, mexiletine, propafenone, sotalol); gastrointestinal motility stimulators (cisapride, pimozide, sertindol and tricyclic antidepressants). Caution should be exercised when using the drug against the background of conditions that are risk factors for QT interval prolongation (hypokalemia, hypomagnesemia).

The interval between taking MAO inhibitors and Reduxin should be at least 2 weeks.

The association between taking Reduxin and the development of primary pulmonary hypertension has not been established, but given the well-known risks of the drugs in this group, special attention should be paid to symptoms such as progressive dyspnea (impaired breathing), chest pain, and edema in the legs during regular medical monitoring.

Impact on driving and operating machinery

The use of Reduxin® may limit the patient’s ability to drive and operate machinery.

Contraindications

– presence of organic causes of obesity (e.g., hypothyroidism);

– serious eating disorders (anorexia nervosa or bulimia nervosa);

– mental illness;

Gilles de la Tourette syndrome (generalized tics);

– concomitant use of MAO inhibitors (e.g., phentermine, phenfluramine, dexfenfluramine, ethylamphetamine, ephedrine) or their use for 2 weeks prior to the prescription of Reduxin®; use of other CNS-acting drugs (e.g., antidepressants, neuroleptics) Drugs prescribed for sleep disorders containing tryptophan, as well as other drugs of central action for weight loss. – CHD, decompensated chronic heart failure, congenital heart disease, peripheral artery occlusive disease, tachycardia, arrhythmias, cerebrovascular disease (stroke, transient cerebrovascular events);

– uncontrolled arterial hypertension (BP over 145/90 mm Hg).Hg).

– thyrotoxicosis;

– severe liver function disorders;

– severe renal function disorders;

– benign prostatic hyperplasia;

– pheochromocytoma;

– closed-angle glaucoma;

– established drug, drug or alcohol dependence;

– pregnancy;

– lactation (breastfeeding);

– childhood and adolescence under 18 years of age;

– older than 65 years of age;

– established hypersensitivity to sibutramine or other components of the drug.

With cautiousness the drug should be prescribed in the following conditions: history of arrhythmias, chronic circulatory failure, coronary artery disease (including in anamnesis), cholelithiasis, arterial hypertension (controlled and in anamnesis), neurological disorders, including mental retardation and seizures (including in anamnesis), liver and/or kidney function abnormalities of mild to moderate severity, motor and verbal tics in anamnesis.

Side effects

Side effects, depending on the impact on organs and organ systems are as follows (often – >10%, sometimes – 1-10%, rarely – < 1%).

On the CNS and peripheral nervous system:often – dry mouth, insomnia; sometimes – headache, dizziness, anxiety, paresthesias, as well as changes in taste; in single cases – back pain, depression, drowsiness, emotional lability, anxiety, irritability, nervousness, seizures.

One patient with schizoaffective disorder, which was presumed to exist before treatment, developed acute psychosis after treatment.

Cardiovascular system:sometimes tachycardia, palpitations, increased BP, and vasodilation. A moderate rise in resting BP by 1-3 mm Hg and a moderate increase in heart rate by 3-7 beats per minute have been observed. In some cases, more pronounced elevations of BP and HR are not excluded. Clinically significant changes in BP and pulse rate are registered predominantly at the beginning of treatment (in the first 4-8 weeks).

Digestive system disorders:often – loss of appetite, constipation; sometimes – nausea, exacerbation of hemorrhoids. With a tendency to constipation in the early days it is necessary to control the evacuatory function of the intestine. If constipation occurs, stop taking it and take a laxative. In isolated cases, abdominal pain, paradoxical increase in appetite, transient increase in the activity of liver enzymes.

Dermatological reactions:sometimes – sweating; in single cases – skin itching, purpura Schoenlein-Henoch (hemorrhages in the skin).

In general:In single cases the following adverse clinically significant events have been described: dysmenorrhea, edema, flu-like syndrome, thirst, rhinitis, acute interstitial nephritis, bleeding, thrombocytopenia.

Withdrawal reactions, such as headache or increased appetite, are rare. There is no evidence of withdrawal, withdrawal syndrome, or mood disorders after treatment.

The most frequent side effects occur at the beginning of treatment (in the first 4 weeks). Their severity and frequency decrease over time. Side effects are generally mild and reversible.

Overdose

There are very limited data on sibutramine overdose. In case of overdose, the patient should consult a physician.

Symptoms: there may be an increase in the severity of side effects. Specific signs of overdose are unknown.

Treatment: intake of activated charcoal, gastric lavage, symptomatic therapy, in case of increase in BP and tachycardia – prescription of beta-adrenoblockers. There is no special treatment or specific antidotes. It is necessary to perform general measures: ensure free breathing, monitor the state of the cardiovascular system, as well as, if necessary, conduct supportive symptomatic therapy. The effectiveness of forced diuresis or hemodialysis has not been established.

Pregnancy use

The drug should not be used in pregnancy due to the lack of a sufficiently conclusive number of studies on the safety of fetal effects of sibutramine.

Women of childbearing age should use contraceptives while taking Reduxin.

Reduxin® should not be used while breastfeeding.